Urethritis is an inflammation of the urethra in men and women, commonly caused by a bacterial infection and considered to be a sexually transmitted disease. Two main forms of bacterial urethritis are recognized, based on the causative agent: gonococcal urethritis (GU) and non-gonococcal urethritis (NGU). GU is due to a Neisseria gonorrhoeae infection, while NGU may be caused by one or more of: Chlamydia trachomatis, Ureaplasma urealyticum, Mycoplasma hominis, Mycoplasma genitalium, or Trichomonas vaginalis. Co-infections by Neisseria gonorrhoeae and Chlamydia trachomatis are also seen. The common occurrence of recurrent infection and the emergence of antimicrobial resistance in the pathogens causing urethritis demonstrate the need for a single, broadly active drug for management of this STD (Centers for Disease Control and Prevention. Increases in fluoroquinolone-resistant Neisseria gonorrhoeae-Hawaii and California, 2001. Morbidity Mortality Weekly Rpt. 51: 1041-1044 (2002); Centers for Disease Control and Prevention. Update to CDC's sexually transmitted diseases treatment guidelines, “Fluoroquinolones no longer recommended for treatment of gonococcal infections.” Morbidity Mortality Weekly Rpt. 56: 332-336 (2006); Merchant et al., Int. J. STD AIDS 20:534-539 (2009); Palmer et al., J. Antimicrob. Chemother. 62:490-494 (2008); Roberts et al., Antimicrob. Agents Chemother. 43:1367-1372 (1999); Roblin et al., Antimicrob. Agents Chemother. 42:194-196 (1998)). Because of sexual practices, two of the bacterial species associated with urethritis, namely Neisseria gonorrhoeae and Chlamydia trachomatis, can also cause infections of the throat, and passage through the birth canal can cause infections in infants. Trachoma conjunctivitis in children is a leading cause of blindness in the world (Burton et al., The global burden of trachoma: a review. PLoS Negl Trop Dis. 3(10):e460 (2009)). Therefore, drugs effective in the treatment of urethritis would also be expected to have efficacy in the treatment of ocular and pharyngeal infections caused by Neisseria gonorrhoeae and/or Chlamydia trachomatis. 
Fusidic acid (FA) is a tetracyclic triterpenoid or fusidane (steroidal) antibiotic derived from the fungus Fusidium coccineum that inhibits bacterial protein synthesis. FA is effective against gram-positive bacteria such as Staphylococcus species and Corynebacterium species (L. Verbist, J. Antimicro. Chemo. 25, Suppl. B, 1-5 (1990); A. Bryskier, Fusidic Acid, Chapter 23, in Antimicrobial Agents: Antibacterials and Antifungals (Andre Bryskier, Ed., ASM Press, Washington, USA, 2005)). FA also has moderate activity against Group A beta-hemolytic streptococci, including Streptococcus pyogenes (L. Verbist, J. Antimicro. Chemo. 25, Suppl. B, 1-5 (1990); A. Bryskier, Fusidic Acid, Chapter 23, in Antimicrobial Agents: Antibacterials and Antifungals (Andre Bryskier, Ed., ASM Press, Washington, USA, 2005); Skov et al., Diag. Micro. Infect. Dis. 40:111-116 (2001)).
FA was developed for clinical use in the 1960s and it is approved for human use outside of the United States, such as in the UK, Canada, Europe, Israel, Australia and New Zealand. It is typically prescribed at doses of 500 mg TID for treating skin and skin structure infections caused by Staphylococcus aureus (A. Bryskier, Fusidic Acid, Chapter 23, in Antimicrobial Agents: Antibacterials and Antifungals (Andre Bryskier, Ed., ASM Press, Washington, USA, 2005); Collignon et al., Int'l J. Antimicrobial Agents 12:S45-S58 (1999); D. Spelman, Int'l J. Antimicrobial Agents 12:S59-S66 (1999)), although some physicians have routinely prescribed the compound at 500 mg BID for treating skin and skin structure infections due to the long half-life of the compound (Fusidic Acid, in Principles and Practice of Infectious Diseases, 6th ed. (Mandell et al. eds., Elsevier, 2006)).
Treatment using FA has been well studied and it is generally regarded as safe when administered to humans, as evidenced by the fact that the drug has been in continuous use since 1968 in various parts of the world. There are, however, several characteristics of FA that have suggested against the use of the drug against a wider spectrum of bacteria and in the treatment in additional types of infection. For example, approved dosing regimens have been shown to select for bacterial resistance, such as in S. aureus. Approved dosing regimens provide low multiples of the MIC and as a result, S. aureus resistant mutants can be selected after the first day of dosing. Once resistance has developed, FA is not effective against the resistant strains. Resistance is reported to occur if FA is used as a single drug as the resistance frequency at 4 and 8 times the MIC is in the range of 10−6 or 10−8 (Evans et al., J. Clin. Path. 19:555-560 (1966); Hansson et al., J. Mol. Biol. 348:939-949 (2005), Jensen et al., Acta Pathol Microbiol Scand. 60:271-284 (1964); Besier et al., Antimicrob. Agents Chemo., 49(4):1426-1431 (2005); Gemmell et al., J. Antimicrobial Chemo. 57:589-608 (2006); Howden et al., Clin. Infect. Disease 42:394-400 (2006)).
The dosage of the drug cannot be simply increased as a means of avoiding development of resistance. It is difficult to achieve high concentrations of free (unbound) FA in the blood due to the substantial protein binding of the drug (approximately 95-97%) (K. Christiansen, International Journal of Antimicrobial Agents 12:S3-S9 (1999); Coutant et al., Diagn Microbiol Infect Dis 25:9-13 (1996); D. Reeves, J. Antimicrob. Chemo. 20:467-476 (1987); J. Turnidge, Int'l J. Antimicrobial Agents 12:S23-S34 (1999); Rieutord et al., Int'l J. Pharmaceutics 119:57-64 (1995)). Moreover, high dosages of FA are not well-tolerated by patients receiving the drug. High doses of FA (e.g., 1 gram TID) are required if the drug is to be used in the treatment of bone and joint infections, less susceptible bacteria and other serious infections. However, treatment regimens using high doses of the drug induce nausea and vomiting and are rejected by patients (Fusidic Acid, in Principles and Practice of Infectious Diseases, 6th ed. (Mandell et al. eds., Elsevier, 2006); K. Christiansen, International Journal of Antimicrobial Agents 12:S3-S9 (1999); Nordin et al., Eur. J. Clin. Res. 5:97-106 (1994)).
In view of the tremendous costs associated with the de novo development of new anti-bacterials, expanding the indications for drugs that have already been demonstrated to be safe and effective is strongly needed. Finding new uses and means for administering FA would broaden the population of bacterial infections against which FA could be used and thus meet this need.